scholarly journals Mechanotransduction in Musculoskeletal Tissue Regeneration: Effects of Fluid Flow, Loading, and Cellular-Molecular Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yi-Xian Qin ◽  
Minyi Hu
Keyword(s):  
Fluid Flow ◽  
Bone Loss ◽  
Mechanical Loading ◽  
Tissue Regeneration ◽  
Underlying Mechanism ◽  
Bone Adaptation ◽  
Bone Tissue Regeneration ◽  
Molecular Pathways ◽  
Musculoskeletal Tissue ◽  
Mechanical Signals

While mechanotransductive signal is proven essential for tissue regeneration, it is critical to determine specific cellular responses to such mechanical signals and the underlying mechanism. Dynamic fluid flow induced by mechanical loading has been shown to have the potential to regulate bone adaptation and mitigate bone loss. Mechanotransduction pathways are of great interests in elucidating how mechanical signals produce such observed effects, including reduced bone loss, increased bone formation, and osteogenic cell differentiation. The objective of this review is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology. We discussed the potential for mechanical loading to induce dynamic bone fluid flow, regulation of bone adaptation, and optimization of stimulation parameters in various loading regimens. The potential for mechanical loading to regulate microcirculation is also discussed. Particularly, attention is allotted to the potential cellular and molecular pathways in response to loading, including osteocytes associated with Wnt signaling, elevation of marrow stem cells, and suppression of adipotic cells, as well as the roles of LRP5 and microRNA. These data and discussions highlight the complex yet highly coordinated process of mechanotransduction in bone tissue regeneration.

scholarly journals The Skeletal Cellular and Molecular Underpinning of the Murine Hindlimb Unloading Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyanka Garg ◽  
Maura Strigini ◽  
Laura Peurière ◽  
Laurence Vico ◽  
Donata Iandolo
Keyword(s):  
Bone Loss ◽  
Mechanical Loading ◽  
Weight Bearing ◽  
Bone Adaptation ◽  
Hindlimb Unloading ◽  
Molecular Pathways ◽  
Long Bones ◽  
Confounding Factors ◽  
Environmental Temperatures

Bone adaptation to spaceflight results in bone loss at weight bearing sites following the absence of the stimulus represented by ground force. The rodent hindlimb unloading model was designed to mimic the loss of mechanical loading experienced by astronauts in spaceflight to better understand the mechanisms causing this disuse-induced bone loss. The model has also been largely adopted to study disuse osteopenia and therefore to test drugs for its treatment. Loss of trabecular and cortical bone is observed in long bones of hindlimbs in tail-suspended rodents. Over the years, osteocytes have been shown to play a key role in sensing mechanical stress/stimulus via the ECM-integrin-cytoskeletal axis and to respond to it by regulating different cytokines such as SOST and RANKL. Colder experimental environments (~20–22°C) below thermoneutral temperatures (~28–32°C) exacerbate bone loss. Hence, it is important to consider the role of environmental temperatures on the experimental outcomes. We provide insights into the cellular and molecular pathways that have been shown to play a role in the hindlimb unloading and recommendations to minimize the effects of conditions that we refer to as confounding factors.

Induced Intramedullary Pressure by Dynamic Hydraulic Stimulation and Its Potential in Attenuation of Bone Loss

2011 ◽  
Author(s):  
M. Hu ◽  
J. Cheng ◽  
S. Ferreri ◽  
F. Serra-Hsu ◽  
W. Lin ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Bone Loss ◽  
Bone Adaptation ◽  
Dependent Manner ◽  
Hydraulic Stimulation ◽  
Flow Coupling ◽  
Bone Fluid Flow ◽  
Intramedullary Pressure ◽  
New Treatments

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.

Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent

2001 ◽  
Vol 281 (5) ◽  
pp. C1635-C1641 ◽  
Author(s):  
Seth W. Donahue ◽  
Christopher R. Jacobs ◽  
Henry J. Donahue
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Mechanical Loading ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Bone Adaptation ◽  
Calcium Oscillations ◽  
Loading Frequency ◽  
Spontaneous Oscillations ◽  
Stress Dependent

Bone adaptation to mechanical loading is dependent on age and the frequency and magnitude of loading. It is believed that load-induced fluid flow in the porous spaces of bone is an important signal that influences bone cell metabolism and bone adaptation. We used fluid flow-induced shear stress as a mechanical stimulus to study intracellular calcium (Ca[Formula: see text]) signaling in rat osteoblastic cells (ROB) isolated from young, mature, and old animals. Fluid flow produced higher magnitude and more abundant [Ca2+]ioscillations than spontaneous oscillations, suggesting that flow-induced Ca[Formula: see text] signaling encodes a different cellular message than spontaneous oscillations. ROB from old rats showed less basal [Ca2+]i activity and were less responsive to fluid flow. Cells were more responsive to 0.2 Hz than to 1 or 2 Hz and to 2 Pa than to 1 Pa. These data suggest that the frequency and magnitude of mechanical loading may be encoded by the percentage of cells displaying [Ca2+]ioscillations but that the ability to transduce this information may be altered with age.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

Bifunctional hydrogel for potential vascularized bone tissue regeneration

2021 ◽  
pp. 112075
Author(s):  
Bipin Gaihre ◽  
Xifeng Liu ◽  
Linli Li ◽  
A. Lee Miller ◽  
Emily T. Camilleri ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Tissue Regeneration ◽  
Vascularized Bone

scholarly journals Size Effects in Finite Element Modelling of 3D Printed Bone Scaffolds Using Hydroxyapatite PEOT/PBT Composites

Mathematics ◽  
2021 ◽  
Vol 9 (15) ◽  
pp. 1746
Author(s):  
Iñigo Calderon-Uriszar-Aldaca ◽  
Sergio Perez ◽  
Ravi Sinha ◽  
Maria Camara-Torres ◽  
Sara Villanueva ◽  
...  
Keyword(s):  
Finite Element ◽  
Additive Manufacturing ◽  
Tissue Regeneration ◽  
Finite Element Modelling ◽  
Bulk Material ◽  
Bone Tissue Regeneration ◽  
Patient Specific ◽  
Design Factor ◽  
Element Modelling ◽  
Uncertainty Sources

Additive manufacturing (AM) of scaffolds enables the fabrication of customized patient-specific implants for tissue regeneration. Scaffold customization does not involve only the macroscale shape of the final implant, but also their microscopic pore geometry and material properties, which are dependent on optimizable topology. A good match between the experimental data of AM scaffolds and the models is obtained when there is just a few millimetres at least in one direction. Here, we describe a methodology to perform finite element modelling on AM scaffolds for bone tissue regeneration with clinically relevant dimensions (i.e., volume > 1 cm3). The simulation used an equivalent cubic eight node finite elements mesh, and the materials properties were derived both empirically and numerically, from bulk material direct testing and simulated tests on scaffolds. The experimental validation was performed using poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) copolymers and 45 wt% nano hydroxyapatite fillers composites. By applying this methodology on three separate scaffold architectures with volumes larger than 1 cm3, the simulations overestimated the scaffold performance, resulting in 150–290% stiffer than average values obtained in the validation tests. The results mismatch highlighted the relevance of the lack of printing accuracy that is characteristic of the additive manufacturing process. Accordingly, a sensitivity analysis was performed on nine detected uncertainty sources, studying their influence. After the definition of acceptable execution tolerances and reliability levels, a design factor was defined to calibrate the methodology under expectable and conservative scenarios.

scholarly journals Analysis of the effects of spaceflight and local administration of thrombopoietin to a femoral defect injury on distal skeletal sites

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariane Zamarioli ◽  
Zachery R. Campbell ◽  
Kevin A. Maupin ◽  
Paul J. Childress ◽  
Joao P. B. Ximenez ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mechanical Loading ◽  
Bone Healing ◽  
Space Flight ◽  
Bone Fracture ◽  
Local Administration ◽  
Systemic Effects ◽  
Human Presence ◽  
Femoral Defect ◽  
Healing Agent

AbstractWith increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space (“Flight”) and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.

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